Delayed Maturation of Regenerating Myelinated Axons in Mice Lacking Neurofilaments

Zhu, Qinzhang; Couillard‐Després, Sébastien; Julien, Jean‐Pierre

doi:10.1006/exnr.1997.6654

Cited by 359 publications

(361 citation statements)

References 82 publications

Supporting

Mentioning

337

Contrasting

Unclassified

Order By: Relevance

“…Actually, Nefl knockout mice showed a morphological change in the peripheral nervous system resembling that in a quail carrying a homozygous nonsense mutation. 19 However, the Nefl knockout mice developed normally and exhibited no overt symptoms. Why NEFL-deficient mice do not show symptoms similarly to the mutant quail remains an open question.…”

Section: Discussionmentioning

confidence: 99%

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

et al. 2009

View full text Add to dashboard Cite

The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four heterozygous missense mutations-Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys--in five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one other patient. All patients had mildly to moderately delayed nerve conduction velocities, possibly caused by a loss of large diameter fibers. This is the first report of a homozygous nonsense mutation of NEFL. Results of our study show that nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

et al. 2009

View full text Add to dashboard Cite

show abstract

“…IFs can provide structural integrity to a cell (Lloyd et al, 1995;Wong et al, 2000;Fuchs and Cleveland, 1998;Yamasaki et al, 1991;Ohara et al, 1993;Eyer and Peterson, 1994;Zhu et al, 1997) due at least in part to the relative physical strength of IFs in comparison to microfilaments and microtubules (Beil et al, 2003;Janmey et al, 1991;Ma et al, 2001;Yamada et al, 2002). However, a role in maintaining cellular integrity is not consistent with the developmental changes seen in subcellular localization of peripherin or with zonal expression of α-internexin during a restricted developmental window.…”

Section: Potential Roles Of Intermediate Filamentsmentioning

confidence: 99%

Cytoskeletal organization of the developing mouse olfactory nerve layer

Akins

Greer

2005

J of Comparative Neurology

View full text Add to dashboard Cite

Olfactory sensory neuron (OSN) axonal extension and targeting occurs within the olfactory nerve layer (ONL) of the olfactory bulb (OB). The ONL can be differentiated into sublaminae: the outer (ONLo), where axons broadly target regions of the OB in tight fascicles, and inner (ONLi), where axons perform final targeting in loosely organized fascicles. During perinatal development cadherin-2 and its binding partner, gamma-catenin, are preferentially expressed by OSN axons in the ONLo versus the ONLi. Given the expression of these cytoskeletal associated molecules, we hypothesized that cytoskeletal elements of OSN axons may be differentially expressed across the ONL. We therefore examined cytoskeletal organization of OSN axons in the ONL, focusing on the day of birth (P0). We show that microfilaments, microtubules, and the intermediate filament (IF) vimentin are homogeneously expressed across the ONL at P0. In contrast, the IFs peripherin and alpha-internexin are preferentially localized to the ONLo at P0, with alpha-internexin expressed by a restricted subset of OSNs. We also show that OSN axons in the ONLo are significantly smaller than those in the ONLi. The data demonstrate that as OSN axons begin to exit the ONLo and target a specific region of the OB there is a down-regulation of cytoskeletal elements and bound extracellular adhesion molecules. The increase in axon diameter may reflect additional mechanisms involved in glomerular targeting or the formation of the large terminal boutons of OSN axons within glomeruli.

show abstract

“…58 However, a lack of NF-L in NF-L knock-out mice does not prevent axonal regrowth after a sciatic nerve crush injury but introduces a delay in maturation of axons. 63 In contrast, NF-L mRNA levels are decreased in the dorsal root ganglion in the early phase of axonal injury following a sciatic nerve lesion in rats. 22,29 This reduction is reversed after 12 weeks of nerve regrowth 23 suggesting that NF-L is more important in the late, than the immediate, phase of axonal regrowth.…”

Section: Relevance Of Increased Neuro®lament Mrna Expression To Cytosmentioning

confidence: 96%

Ovariectomy up-regulates neuronal neurofilament light chain mRNA expression with regional and temporal specificity

et al. 2001

View full text Add to dashboard Cite

AbstractÐEstrogens can in¯uence the survival, plasticity and function of many adult neurons. Many of these effects, such as neurite outgrowth and increased dendritic spine density, are mediated by changes in neuronal cytoskeletal architecture. Since neuro®lament proteins play a key role in the maintenance and remodeling of the neuronal cytoskeleton, we postulated that changes in neuro®lament light chain mRNA may parallel some of the alterations in neuronal architecture which follow bilateral ovariectomy. We measured neuro®lament light chain mRNA levels using a ribonuclease protection assay at two time-points after ovariectomy in mature female rats. One week after ovariectomy, neuro®lament light chain mRNA levels (corrected for glucose-6-phosphate dehydrogenase mRNA) did not differ from sham-operated animals in the ®ve brain regions examined (hypothalamus, striatum, hippocampus, frontal cortex and occipital cortex). Four months after ovariectomy, neuro®lament light chain mRNA levels were similarly unchanged in the hypothalamus and striatum. In contrast, statistically signi®cant increases in neuro®lament light chain mRNA expression were observed in the three regions receiving basal forebrain projections (hippocampus, frontal cortex and occipital cortex). In situ hybridization demonstrated increases in neuro®lament light chain mRNA expression involving subpopulations of smaller medial septal neurons. There also appeared to be an increased number of larger septal neurons following long-term ovariectomy.We propose that atrophic changes involving basal forebrain projection ®bers are followed by compensatory axonal growth by other`intact' basal forebrain neurons. Increased neuro®lament light chain mRNA expression and somatic hypertrophy in medial septal neurons may both be re¯ective of the need to sustain an axonal network which is larger and more complex. In contrast, increased neuro®lament light chain mRNA expression observed in basal forebrain targets following long-term ovariectomy may be re¯ective of compensatory changes taking place in local neurons. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: aging, Alzheimer's disease, axonal cytoskeleton, basal forebrain, hormone replacement therapy, in situ hybridization.The female menopause is characterized by a loss of ovaries as a source of estrogen and progesterone production, resulting in signi®cant declines in levels of these hormones in many older women. 24 Hormone replacement therapy (HRT) with estrogen has been shown to be useful in the prevention of age-related events such as peri-and post-menopausal bone loss. Several recent studies indicate that women receiving HRT tend to have lower rates of Alzheimer's disease (AD) 18,53 than their matched controls. In addition, gonadal steroids (GS) can in¯uence the ability of many cells, including some neuronal populations, to maintain normal structure and function. As a result, there has been a growing interest in exploring the possibility that HRT may prevent AD or, at least, slow its progr...

show abstract

Delayed Maturation of Regenerating Myelinated Axons in Mice Lacking Neurofilaments

Cited by 359 publications

References 82 publications

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

Neurofilament light chain polypeptide gene mutations in Charcot–Marie–Tooth disease: nonsense mutation probably causes a recessive phenotype

Cytoskeletal organization of the developing mouse olfactory nerve layer

Ovariectomy up-regulates neuronal neurofilament light chain mRNA expression with regional and temporal specificity

Contact Info

Product

Resources

About